The purpose of this study is to investigate the role of the polyamines in the development of the secondary palate. Elevated levels of the polyamines have been found in both the hyperplastic and hypertrophic stages of developmental growth in many diverse systems. These higher levels are due to increased activity of theenzymes in the biosynthetic pathway, mainly ornithine decarboxylase and, to a lesser extent, S-adenosyl-L0methionine decarboxylase and they appear to mediate alterations in DNA, RNA and protein synthesis. Inhibitors of polyamine biosynthesis have been found to interfere severely withj further growth and development. Fetal rabbit palates cultured in vitro will be used as model system to examine the role of the polyamines in the fusion process. The concentrations of the polyamines, namely, putrescine, spermidine and spermine, and the activities of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase will be measured in isolated palatal shelves at different stages of development preceding fusion and these levels will be correlated with palatal DNA, RNA and protein synthesis to determine the growth parameters affected. Palatal polyamine concentrations will be decreased in vitro by the use of inhibitors of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase and the effect on palatal fusion in vitro will be determined to establish the physiological significance of these compounds. Nucleic acid and protein synthesis will also be determined allowing the identification of the molecular mechanisms affected by decreasing polyamine concentrations. The palate is a major target for teratogens and an understanding of the basic events controlling palatal growth and fusion is necessary in determining the mechanisms of cleft palate induction. Since the activity of otnithine decarboxylase, the rate limiting enzyme in polyamine synthesis is extremely sensitive to a variety of stimuli, including hormones, drugs and diet, it represents a possible site for teratogenic action.